Posted
by
ScuttleMonkey
on Friday September 25, 2009 @03:17PM
from the justification-for-more-sleep dept.

sonnejw0 writes "NewScientist is reporting a link between sleep deprivation and Alzheimer's Disease via an increased amyloid-beta plaque load thought responsible for a large part of the symptoms of the disease, in mice. Medication to abrogate insomnia reduced the plaque load. Also discussed is a recently discovered sleep cycle of amyloid-beta deposition in the brain, in which levels decrease while asleep. 'Holtzman also tried sending the mice to sleep with a drug that is being trialled for insomnia, called Almorexant. This reduced the amount of plaque-forming protein. He suggests that sleeping for longer could limit the formation of plaques, and perhaps block it altogether.'"

Well, it doesn't. Reagan was noted as a not a hard working president, early to bed, late to rise type guy. Yet, he died of this disease. Of course some people think he was a rat, so maybe the analogy applies.

Could delaying the inevitable onset of Alzheimer's be the biological function of sleep? Last I heard, the purpose of sleep wasn't entirely clear, and there were anecdotal reports of people basically eliminating it with drugs, sometimes with little ill-effect. I've long been of the opinion that if wakefullness promoting agents don't have short-term effects, there must be a longer-term negative impact, because if there weren't, the body would synthesise something similar, at least in people who are sufficiently well-fed not to mind the extra energy usage. Sleeping is basically a good chance to get eaten.

It's going to be a long time before we find out if regular modafinil users get early Alzheimer's.

P.S. It's been over an hour, and it still isn't possible to reply to this article. I'll post this when Slashdot works. I predict about 30 people claiming First Post.

Could delaying the inevitable onset of Alzheimer's be the biological function of sleep? Last I heard, the purpose of sleep wasn't entirely clear, and there were anecdotal reports of people basically eliminating it with drugs, sometimes with little ill-effect. I've long been of the opinion that if wakefullness promoting agents don't have short-term effects, there must be a longer-term negative impact, because if there weren't, the body would synthesise something similar, at least in people who are sufficiently well-fed not to mind the extra energy usage. Sleeping is basically a good chance to get eaten.
It's going to be a long time before we find out if regular modafinil users get early Alzheimer's.

I'd credit your theory; however there has been some research that shows Caffeine can also act against Alzheimer's. When consumed regularly it appears to slow it's progress as well as somewhat mitigating the symptoms.

Of course, the term "wakefulness promoting agent" is used to distinguish drugs like modafinil from traditional stimulants like caffeine. Going without sleep with caffeine usually means you have to catch up, and, in my own experience, doesn't stop you getting stupider after several hours. Modafinil supposedly allows one to stay up all night, functioning normally, and only require the normal amount of sleep the night after they come off it.

Of course, the term "wakefulness promoting agent" is used to distinguish drugs like modafinil from traditional stimulants like caffeine.

I figured the phrase "wakefulness promoting agent" is used mainly to distinguish drugs like modafinil from the traditional US Schedule II stimulants amphetamine and methylphenidate, possibly to avoid any negative connotations associated with the word stimulant and these drugs. I've seen claims that modafinil isn't even a stimulant at all [google.com].

Well, the Schedule II rating is a very easy way to quit getting prescribed. Amphetamines work, and they're cheap. But you *can* get high with them, so we have to restrict the crap out of them. [Insert drug war rant.]

OTOH, they're not without downsides. See, amphetamines work by increasing the catecholamine (particularly norepinephrine) levels in the brain. They push the catecholamines out of the storage vesicles into the synapses. (FWIW, cocaine works by preventing neurotransmitters from being absorbe

There is no such thing as sleep deprivation without short term ill-effects. We know that cognitive ability declines with a lack of sleep, even if it's a small lack of sleep ever night over an extended period of time. Your cognitive ability and reaction time will continue to decline until you start getting complete sleep. In fact, after a few weeks, people with sleep deprivation begin to perceive that they're "getting used to it" and are going back to normal in spite of their continued decline.

I have zero proof, but I've always figured sleeping was simply a low power state to go into since we're highly optimized to operate in well lit conditions. Then the body then found some other useful things it could do while sleeping, like imprinting recently learned patterns in the brain.

Humans are conditioned for being awake in the day time, but there is no reason to believe that this has anything to do with the need for sleep other than the fact that when we sleep is regulated by the circadian rhythm which is controlled by light exposure. However, all mammals need sleep whether they are awake in the day, nocturnal, or sea mammals.

I suspect sleeping has a higher level function as well, like getting rid of all the crap you accumulate in your head throughout the day. Maybe some (perhaps non-essential, just useful) chemicals in our brain tend to run out when awake, and sleep is needed to restock them.

However, awake is only one state of mind out of many, it'd be foolish to disregard most of them. (I don't consider "auto-pilot on the highway" awake, for example.)

Not necessarily. Wandering around in the open is probably a lot more dangerous than being holed up in a lair - especially if your sensory organs are optimized for night and it is day or vice versa. Plus, animals and people are very highly attuned to certain noises while asleep - basically if it sounds like something is approaching or entering the lair most animals will quickly transition from sleep to fully awake.

It could just be that, evolutionary speaking, there wasn't much to do at night and thus we rest half the day to save energy.

Circular reasoning. Doesn't fit. If we didn't have sleep in the first place, there would be plenty to do at night... (and plenty of mammals/birds/fish have adaptations to demonstrate that it is perfectly reasonable to function during the night.)

Think of it differently: if the evolutionary driver for sleep was simply that there "wasn't much to do at night" -- well, that doesn't make se

Could delaying the inevitable onset of Alzheimer's be the biological function of sleep? Last I heard, the purpose of sleep wasn't entirely clear

What? No. There are at least two functions of sleep that I know of: one is cleaning up misshapen proteins that accumulate during the day (and may be what causes tiredness). The other is transcription of short-term memory into long-term memory. Evolutionarily speaking, nobody ever lived long enough to get Alzheimers. Those who did wandered off into the tundra and didn't burden the tribe any longer.

You first point is (seemingly) correct. Sleep is not evolution's way of preventing Alzheimer's Disease. Your second point is incorrect.

Healthy old folks are directly beneficial to social groups. They remember how to solve problems. They can take care of grandchildren while the parents are off gathering food. And many social groups had old folks. Sure, most people didn't live to get very old. But some did.

Healthy old folks are directly beneficial to social groups. They remember how to solve problems. They can take care of grandchildren while the parents are off gathering food. And many social groups had old folks. Sure, most people didn't live to get very old. But some did.

That's absolutely true of grandparents, but we're talking about great-great grandparents here, from a bio-evolutionary standpoint.

That's a non-sequitor. Grandparents or great-grandparents is irrelevant.

Age = wisdom. Most people didn't live past 60 back in the day, but if somebody just so happened to do so, it's was something to look up to and try to duplicate. Believe it or not, people used to value the elderly, and in many parts of the world, they still do.

That's a non-sequitor. Grandparents or great-grandparents is irrelevant.

Of course it's relevant, it's the law of diminishing returns. Does a 75 year old really impart so much more wisdom to a tribe than a 60 year old does? A 90-year old? Does that wisdom imparted provide significant enough benefit to weigh against the resource requirements in order to achieve reproduction and child-rearing age improvements, say 35 years or so for an average lifespan?

The full purpose behind sleep is still unclear. We know a fair amount of what happens during sleep, but we don't understand why it has to take place while we sleep or why sleep has multiple stages and why we cycle through them twice each night. Tiredness is caused by a chemical regulated by the Circadian Rhythm.

Right, the release of melatonin will make you feel sleepy right now, but what causes the Circadian Rhythm to establish/maintain? I can't seem to find the right search on pubmed tonight, but there was recent research to suggest that an accumulation of misfolded proteins during the course of the day is at least one of the mediators, and that those are cleaned up during the rest cycle, making the rhythm self-establishing.

I can't speak with too much authority on the topic of Circadian Rhythm regulation, and I am sure there are several factors involved. What I do know from working in the sleep therapy industry is that one of the primary factors is light exposure which, at least for humans, explains why we tend to be awake in the day, and changing to night shifts is extraordinarily difficult for most people. By my thinking, accumulation of misfolded proteins may actually be a good explanation for the irregularities in the Ci

There are at least two functions of sleep that I know of: one is cleaning up misshapen proteins that accumulate during the day (and may be what causes tiredness). The other is transcription of short-term memory into long-term memory.

Sleep also serves an important economic function. Just ask the proprietor of any business in the bedding industry, the hotel industry, the sleeping car manufacturing industry.... Where would our GDP be without sleep creating demands for all those goods?

Now I wait and see if anyone tries to take me seriously. It always happens when you make a deliberately stupid comment.

Sleep also serves an important economic function. Just ask the proprietor of any business in the bedding industry, the hotel industry, the sleeping car manufacturing industry.... Where would our GDP be without sleep creating demands for all those goods?

On the other hand, if you didn't need sleep, you could squeeze 120 hours of work into a 5-day workweek. Think of how much that would benefit the shareholders!

Now I wait and see if anyone tries to take me seriously. It always happens when you make a delibera

This is yet another worthless study given credence by being run on Slashdot. Like the one about how sugar is going to kill us. And obesity causes alzheimers, a study done on less people than attend your average wedding. And how gamers aren't adolescents. You know, the study that only looked at results in people over 19.

It's another example of preconceptual science. They decide the conclusion they want, then discard all the evidence that contradicts it.

Sleep does all sorts of things. Two of the biggies are long term potentiation and basic repair. Scrubbing accumulated beta amyloid or precursors fits in the second category.

Anti-sleep drugs might let you get less sleep but they may also interfere with those processes that occur during sleep - you don't learn things long term as well and your brain and body wear out faster.

Alan MacDonald, M.D., is a pathologist affiliated with St. Catherine of Siena Medical Center in Smithtown, New York. His current research is concentrated on developing what he refers to as a new biology for Lyme disease, including the use of special DNA probes to detect Borrelia DNA in spinal fluid and in tissue sections from Alzheimer autopsy tissues.

Through his research, and with the help of other leading researchers in the field of molecular and cellular biology, Dr. MacDonald is pioneering a broader understanding about the behavior of Borrelia burgdorferi, the bacteria that causes Lyme disease. He has appeared as an invited lecturer at Lyme symposia, including the ILADS National Scientific Meetings and Columbia University/Lyme Disease Association conferences in Philadelphia, PA, where he presents the findings from his explorations into the connection between Borrelia spirochetal infection and Alzheimer's disease.

Dr. Alan MacDonald: "Using the syphilis model, I began to study some autopsied brains, and found that I was able to identify spirochetes in autopsied brain tissue in the hippocampus, which is one of the areas that Alzheimer's disease tends to target in every patient. I was able to grow spirochetes from autopsied Alzheimer's brain tissue, and stain the spirochetes with special monochromal antibodies, through the techniques I learned and developed through the study of stillborn babies with Lyme disease. And those two positive results made me think even more strongly that some Alzheimer's might be like syphilis, a late manifestation of the bacterial infection in the brain, not to say that all Alzheimer's disease is related to Lyme disease, but some."

Not enough is known about Lyme Disease and its relation to Alzheimer's, ALS, MS, Fybromyalgia, etc. But, you can be sure Dr. MacDonald will be at the forefront.

That'd be pretty great. the number of tickbites is certain to decrease, and, if it's identified as a major thread, can certainly be avoided almost entirely. But it's only been published in a single paper called "Medical Hypotheses" and there are a number of other diseases mentioned as possible causes: "In both AD and/or the tSEs, transmissible agents and infectious proteins have been postulated to be aetiological factors [4], [8], [11], [12] and [13]. These include bacteria such as Chlamydia pneumoniae [14]

Why is it that anyone talking about fringe theory stuff feels the need to use the entire name and title of their favourite researcher? Most academics would say something like "there's been work done on blah, such as blah by MacDonald et. al". But the questionable stuff is always "Dr. Alan MacDonald did this, and Dr. Alan MacDonald did this...."

You might want to tone that back a bit. It makes it sound as if you can't believe an actual person with qualifications is working on it. Oh, and it also makes it

Could this plaque, and its base cause of sleep deprivation also be the cause of some mental illnesses? I have heard that Alzheimer's Disease resembles both Schizophrenia and Bipolar. Maybe this might have implications for those tragic diseases.

I dunno, I'm not so sure I'd call those diseases tragic. I find the rest of the world's 16 hr waking days terribly boring and pity their lack of creativity and productivity. Granted some people don't cope well with BP and Schizophrenia and they make the news (so to speak) but many people manage well and use it to their advantage.

I do hope that only sleeping 3.5 hrs a day (on average) for my entire life won't have the detrimental payback of Alzheimer's. But, then again, there is a price to pay for everyth

My husband suffers from severe sleep aponea, it was misdiagnosed for over a decade, firstly as a bi-polar disorder, followed be epillepsy which for some reason resisted treatment as they upper the doasge on his meds every 6 months. When he was eventually diagnose, the specialist said it was likely he had had no level 3 or 4 sleep in over a decade.

By the time he was diagnosed, he was hallucinating, hearing voices and seeing things that didn't happen, passing out or having vacant seizures on almost a daily ba

No. Antipsychotics are generally dopamine receptor blockers. While this does produce sedation (and weight gain), they are not sleeping pills. Interestingly enough, the first antipsychotics to be discovered were found by projects that were trying to find antihistamines, which were sedative because they were (accidentally) also anticholinergics;

I don't know much technical details, but I know of this [wikipedia.org] one because I've taken it. From the article:

Seroquel...an atypical antipsychotic...sometimes used off-label...to treat such conditions as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression...and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.

Take a look at that. Sleep is a key point, if not the key point of many of the disorders listed above. Even alcoholism, because alcohol prevents good sleep. You take the drug so that you pass out before you reach for the bottle. The good sleep alleviates symptoms which cause one to reach for the bottle in the first place. So on and so forth.

Taking the drug is exactly like slipping into the relief of a hyp [wikipedia.org]

I'm a practicing physician with a strong interest in pharmacology. I do know the technical details. Unfortunately, I apparently suck at making a point, because this is the second comment in this thread that I've had fall victim to my unclear phrasing.

To amplify: They are sedative, but they are most assuredly not glorified sleeping pills - a benzodiazepine, a barbiturate, or a central anticholinergic would be what people think of as sleeping pills, and none of those would work.

I went 2-3 days w/out sleep in college, now(15 years later) I can hardly make it through the day without a nap.7 hours a night is my minimum or I am definitely off my A Game that day. Some nights I need 10.

I'm suspecting sleep apnea [sleepapnea.org] for myself. Sleepiness, brain fog, slow thinking, lack of willpower, even mild depression... all can be caused by it. I'm seeing a doctor about it next week. I wonder if it ties into Alzheimer's now. My grandfather had both.

I had the same thing as you - in college, I could go more than a day without sleep. I'd definitely be dragging that second day, but I could do it. After college, and as time wore on, I found that I just needed more and more sleep. On weekends, I would sometimes get 12+ hours of sleep - and I'd still be tired!! I'd sometimes take naps on weekend afternoons.

For me, the problem was that I had obstructive sleep apnea. That's where you stop breathing when you fall asleep (your brain wakes you up just enough that you start breathing again, but not enough that you become aware that you woke up.) Most people who have sleep apnea aren't even aware they have a problem, they just assume you should be tired all the time.

I was finally diagnosed last year, and I did a sleep study**. They gave me a CPAP machine - I wear the mask whenever I sleep, and the CPAP machine pushes air into me. Effectively, it's inflating my airway so it doesn't close during the night. I'm a totally different person now! I don't need naps, and I sleep about 7-8 hours a night before I wake up normally.

If you're feeling the same way (naps during the day, needing more time every night to get rested) you might want to see a sleep specialist and ask for a sleep study.

My [twin] brother reported similar symptoms as you, and I eventually convinced him to see his doctor about it. Turns out, he also has apnea, got a CPAP, and is much better.

** For you fellow CPAP users out there, let's compare numbers: I had 57 sleep disruptions per hour, and my CPAP pressure is 14, no EPR.

It happens to me every so often. Occasionally, I will actually wake up, but it's rare, since I don't have this problem every night. The key to knowing when it happens is when I wake up tired. And when I wake up tired, I have felt the sensation of not breathing right before I consciously wake up.

From what I remember my dr telling me, the mouth appliance works for like 5% of the people out there, and addresses a specific origin of apnea. I think it only works with very mild snoring/apnea though.

My score of 57/hr means I have quite severe apnea. The mouth appliance would never work on me, even if I happened to have that specific apnea that the appliance addresses.

The three pillars to good health: sleep, nutrition, and exercise. If one of them is missing, the rest all goes downhill.

With the old people I've talked to who need less sleep, it seems they are also at the same time not quite getting the exercise and proper nutrition they need to keep their body sustained. Sleeping is work for your body, it spends the time in repairs. If you don't have the right nutrients, it's harder.

Sometime try fasting for a couple days and see how it affects your sleep. Instead of skipping food completely, you can try going on a 900 calorie diet for a while. Pretty soon you will find that your don't sleep as long, but that you aren't as well rested either. The worst is when you sleep a full six hours, but find you feel as though you haven't slept at all.

If you don't eat all the nutrients you need, say you don't eat enough vegetables, the same thing will happen to you, but on a longer scale. It may take years for the lack of broccoli in your diet to show up in your body, but eventually it will, and you will feel it. That happens to a lot of old people.

People with certain neurological conditions (like myself) need more sleep than the average person because we have to work harder to do the same physical/mental tasks as everyone else. Many people can function just fine on a regular basis with just 6 hours of sleep but I need at least 8 per night or my ability is impaired even more. Fortunately, I work at home and can take a nap or just rest for a little while anytime I need to.

Yeah-- I was an architecture student. First night without sleep no problem. Second night... a little wired and not allowed to play witty xacto knives. Walking home after the third night, nothing but halucinations. Curse you, dr. Pepper!

I am as well, I get 4-6 hours most nights when I'm NOT having an insomnia episode and both of my grandmothers have Alzheimer's. I think my only hope is that medical science will have evolved enough in the next 30 years that they will have some way to remove the plaques before they start to rob me of my cognitive functions. I have already told my kids that they are to take me on a hike into the backwoods of Yellowstone in the fall if I ever get to the point where they want to put me in a home, at least there

I have to say, I like reading this kind of story, but they are so far beyond my area of expertise that I can't ever say anything except "wow, that's interesting."

I guess I can try for the fake-pretending-I-understand, "an increased amyloid-beta plaque load?? Why of course! The meta-prozoids all make sense now!!" OR vaguely humorous, "Why plaque? That only grows on teeth!!!"

Anyway, just saying that even though I don't always comment on these stories, that doesn't mean I don't find them interesting. Th

NOW you tell me...my default behavior for any Slashdot story is to go into the comments and search for "phantomfive". If I don't find it, I assume the story must not be very interesting, and I move on to the next one. Now what am I supposed to do? And how many interesting stories have I missed all this time?

Alzheimer's suffers have amyloid-beta plaque deposits in their brains. Usually. Not always.

There are people who have amyloid-beta deposits in the brains. Some of them have dementia, including Alzheimer's. Not all.

Amyloid-beta plaque can be cleared from the brain by immunization. The dementia occurs anyway.:AB42 Immunisation Clears Brain Plaques, Does Not Prevent Dementia...http://www.pslgroup.com/dg/225f1e.htm [pslgroup.com]

Thus, this article should read "Amyloid-Beta Plaque Desposition and Clearing Possibly Associated With Sleep", and any implied link to Alzheimer's saved until the discussion section at the end.

Alzheimer's suffers have amyloid-beta plaque deposits in their brains. Usually. Not always.

There are people who have amyloid-beta deposits in the brains. Some of them have dementia, including Alzheimer's. Not all.

Amyloid-beta plaque can be cleared from the brain by immunization. The dementia occurs anyway.:AB42 Immunisation Clears Brain Plaques, Does Not Prevent Dementia...http://www.pslgroup.com/dg/225f1e.htm [pslgroup.com]

Thus, this article should read "Amyloid-Beta Plaque Desposition and Clearing Possibly Associated With Sleep", and any implied link to Alzheimer's saved until the discussion section at the end.

There is a family of amyloids associated with Alzheimer's and dementia, of which AÃY42 is only one. While AÃY42 is typically the quickest to aggregate, AÃY40 can cause dementia just as easily (though it takes a lifetime to aggregate enough of it).

"... can cause dementia just as easily..." implies a persistent belief in causation despite the reference providing evidence that one of the two obviously is not causative. What can be taken as adequately supported understanding of causation is the fact that Ab40 accumulation (by far the majority of plaque deposit) is seeded by the earlier accumulation of Ab42 (and 43) that forms tendrils much faster, attracting Ab40 out of 'diffuse plaque', the solution of non-tendrilled amyloid beta proteins with a hydro

I wonder what the implications of this are for polyphasic sleep [wikipedia.org] and it's proponents. I've always thought the Uberman schedule (4 hours blocks of time with 30 minute naps) was an interesting idea, though I've never lived a lifestyle that would make it possible.

Okay, so let's give credit - this is a legitimate researcher doing interesting (if highly preliminary) work. From his bio, accessible from TFA, you find that:

We have been assessing CSF and plasma samples from human subjects at the Washington University ADRC and have found that decreased CSF [alpha-beta] and increased tau are harbingers of cognitive decline in cognitively normal elderly.

Which suggests that the increase in CSF beta protein seen in sleep deprivation might actually be a harbinger of protection